Drug & supplement interaction

Sulforaphane + Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine brand names: Tylenol PM, Tylenol PM Ex Strength.

Moderate Interaction
Medically reviewed by · Updated September 2026
The bottom line Moderate

Acetaminophen, Diphenhydramine falls into 2 drug categories that Sulforaphane can interact with; the most serious is rated moderate. Theoretically, sulforaphane might alter the levels and clinical effects of CYP1A2 substrates.

Read the full interaction report
SeverityModerate
LikelihoodPossible
Interactions2
EvidenceD
What do Severity, Likelihood & Evidence mean?
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Interaction report

Sulforaphane and Acetaminophen, Diphenhydramine

These two interact in 2 distinct ways. Each one is explained separately below.

Why Are There 2 Interactions?

Sulforaphane interacts with whole categories of medication. Acetaminophen, Diphenhydramine falls into 2 of those categories, so it can interact with Sulforaphane in 2 different ways. We’ve listed each one below — your overall risk is driven by the most serious of them (Moderate).

Moderate

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES

1 of 2

Why this applies to Acetaminophen, Diphenhydramine

Acetaminophen, Diphenhydramine falls under CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES — the group Sulforaphane interacts with.

Theoretically, sulforaphane might alter the levels and clinical effects of CYP1A2 substrates.
Animal and in vitro research shows that sulforaphane inhibits CYP1A2 enzyme activity. However, its precursor glucoraphanin also appears to increase the expression of the CYP1A2 enzyme, which could lead to increased metabolism of CYP1A2 substrates. These effects have not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the honest picture with Tylenol PM, which combines acetaminophen (a pain and fever reducer) and diphenhydramine (the sleepy antihistamine in Benadryl). Sulforaphane from broccoli may nudge an enzyme called CYP1A2, which helps process certain medications. The tricky part is that lab and animal studies pull in two directions: sulforaphane itself may slow this enzyme, while its precursor may speed it up. So we can't even say cleanly which way it would go.

The good news: none of this has actually been seen in people, and it's based only on test-tube and animal work. Eating broccoli won't be an issue. If you take a concentrated sulforaphane supplement, just mention it to your pharmacist or doctor to be safe.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Barcelo S, Mace K, Pfeifer AM, Chipman JK. Production of DNA strand breaks by N-nitrosodimethylamine and 2-amino-3-methylimidazo[4,5-f]quinoline in THLE cells expressing human CYP isoenzymes and inhibition by sulforaphane. Mutat Res 1998;402:111-20. PubMed
  2. Fimognari C, Lenzi M, Hrelia P. Interaction of the isothiocyanate sulforaphane with drug disposition and metabolism: pharmacological and toxicological implications. Curr Drug Metab. 2008;9(7):668-78. PubMed
  3. Chinnappan SM, George A, Evans M, Anthony J. Efficacy of Labisia pumila and Eurycoma longifolia standardised extracts on hot flushes, quality of life, hormone and lipid profile of peri-menopausal and menopausal women: a randomised, placebo-controlled stud
Moderate

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES

2 of 2

Acetaminophen, Diphenhydramine also falls under CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES.

Theoretically, sulforaphane might increase the levels and effects of CYP2E1 substrates.
In vitro evidence shows that sulforaphane inhibits CYP2E1 enzymes. This interaction has not been reported in humans.
Severity Moderate Likelihood Possible Evidence D

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.

Dr. Brian Staiger, PharmD, BCPS
Dr. Brian Staiger explains PharmD, Clinical Pharmacist

Here's the thinking behind this one. Tylenol PM combines acetaminophen with diphenhydramine (a sedating antihistamine). The acetaminophen part is partly handled by a liver enzyme called CYP2E1, which can turn a small amount of it into a harmful byproduct. In test-tube studies, sulforaphane seems to slow down that enzyme. In theory, less of that toxic byproduct gets made, so this isn't really a recipe for danger.

Honestly, this is a very weak, lab-only signal that has never shown up in real people, and the broccoli on your dinner plate won't move the needle. The bigger thing with Tylenol PM is keeping acetaminophen at safe daily limits and watching for next-day drowsiness from the diphenhydramine. If you're using a concentrated sulforaphane supplement, just run it by your pharmacist.

Contact Dr. Brian directly if you have additional questions on this interaction
References
  1. Fimognari C, Lenzi M, Hrelia P. Interaction of the isothiocyanate sulforaphane with drug disposition and metabolism: pharmacological and toxicological implications. Curr Drug Metab. 2008;9(7):668-78. PubMed

What These Ratings Mean

Every interaction above is graded three ways — here’s the key to each label.

Severity how clinically significant the interaction is
Major

Clinically significant. Avoid the combination, or use only under close professional supervision.

Moderate

Usually worth avoiding or managing — may need monitoring, a dose change, or timing apart.

Minor

Generally not serious. Be aware of it and mention it to your pharmacist.

Likelihood how strong the evidence is that the interaction actually happens in people
  • LikelyWell-controlled human studies have demonstrated the likely existence of this interaction.
  • ProbableInteraction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.
  • PossibleInteraction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists.
  • UnlikelyInteraction has been demonstrated in animal or in lab research but has been shown not to occur in humans.
Evidence the quality of the studies behind the rating (graded A–D)
  • AHigh-quality meta-analysis (quantitative systematic review).
  • BCase-control study.
  • CConsensus.
  • DAnecdotal evidence.

These ratings are for information only. Never start, stop, or otherwise change your therapy before speaking with your provider.

Keep it in perspective

Sulforaphane Also Interacts With Other Medications

Sulforaphane has 721 moderate known drug interactions in our database — the Acetaminophen, Diphenhydramine one above is among them. If you take anything else, check it against the full list below.

Moderate 721 No known interaction 2,109 (incl. Acetaminophen, Diphenhydramine)
Taking anything else?

Check Another of Your Medications Against Sulforaphane

Covers the 2,830 medications we’ve checked against Sulforaphane. Pick one to open its full report.

Everything else you take

See Every Supplement That Interacts With Acetaminophen, Diphenhydramine

This page covers Sulforaphane only. If you take other supplements — a multivitamin, a sleep aid, something for joints — the Acetaminophen, Diphenhydramine page lists 254 supplements it has a documented interaction with, worst first, each one explained.

The most serious there right now: 1,4-butanediol (major), Activated Charcoal (major), Asarabacca (major), Beer (major) and Gamma-hydroxybutyrate (ghb) (major).

By severity: 11 major · 204 moderate · 39 minor.

Open the Acetaminophen, Diphenhydramine interaction page

One more smart check

Taking Sulforaphane as Part of a Dietary Supplement Product? Check It for Interactions

We hold 167 real supplement products containing Sulforaphane, each one broken down to its full ingredient list — and combination products often carry several ingredients besides Sulforaphane. Your product may carry other ingredients that interact with Acetaminophen, Diphenhydramine too, on top of Sulforaphane — and those would not show on this page. Find your product and we’ll check every ingredient on its label:

How much people look this up

Where Sulforaphane and Acetaminophen, Diphenhydramine Sit Against Everything Else

Out of every supplement and medication people look up on HelloPharmacist, here is where these two land this week — and which way each has been moving.

Supplement Sulforaphane
Top 25%

#351 of 1,452 supplements looked up here in the last 7 days

29 days ago today
Medication Acetaminophen, Diphenhydramine
Top 10%

#218 of 2,830 medications looked up here in the last 7 days

29 days ago today

Position among everything looked up on this site, not a measure of how commonly either one is used or how important it is. A supplement can climb this list because of a news story. It counts every request to the page, automated ones included, and nothing here identifies anyone.

Supplement

About Sulforaphane

What is Sulforaphane?

  • Antioxidant support
  • General cellular health
  • Detoxification support
  • Inflammation
  • Skin and aging concerns

Sulforaphane is a natural compound found in broccoli and other cruciferous vegetables that has shown promising antioxidant and anti-inflammatory effects in lab studies, but strong human evidence for most specific health claims is still limited. It is generally well tolerated as part of a vegetable-rich diet, but if you take a concentrated supplement, talk to your pharmacist or doctor first.

Read the full Sulforaphane monograph & all interactions
Keep checking

Other Drugs & Sulforaphane

Browse every other medication we’ve checked against Sulforaphane — both the ones with a known interaction and the ones without. Select any drug for the full detail.

0Major
721Moderate
0Minor
2,108No known interaction
721 Moderate 2,108 No interaction
Moderate

721 interactions

Showing 60 of 721 moderate interactions — see all 721 on the Sulforaphane page.

No interaction 2,108 drugs checked — show the list

We also checked Sulforaphane against these medications and found no known interaction in our sources. Open any page to confirm.

Showing the 60 most looked-up of 2,108 medications checked with no known interaction — see the full Sulforaphane list.

See the full Sulforaphane interactions page
See every supplement checked against Acetaminophen, Diphenhydramine, ranked by severity
Sources

Sources & How We Checked

Interaction details are evidence-graded and sourced from the Natural Medicines database. The medication overview comes from MedlinePlus.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

Keep exploring
Sulforaphane monograph › Uses, safety, and every drug interaction in one place Acetaminophen, Diphenhydramine supplement interactions › Every supplement checked against Acetaminophen, Diphenhydramine, ranked by severity Supplement interaction checker › Check any supplement or product against your medications Browse medications A–Z › Every drug we've checked against herbs & supplements Ask a pharmacist › Free, personal answer from our licensed team
Pharmacist Counseling Corner

Taking Sulforaphane and Acetaminophen, Diphenhydramine Together: Common Questions

Can you take Sulforaphane with Acetaminophen, Diphenhydramine?
There is a moderate interaction, so it may be acceptable with monitoring or timing changes — but check with your pharmacist first. Read the full details on this page and confirm with your pharmacist before combining them.
Why are there 2 interactions listed for Sulforaphane and Acetaminophen, Diphenhydramine?
Acetaminophen, Diphenhydramine belongs to more than one drug category, and Sulforaphane interacts with each of those categories a little differently. We list every one so nothing is missed — your overall risk is driven by the most serious of them.
How serious is the Sulforaphane and Acetaminophen, Diphenhydramine interaction?
We rate it Moderate. This combination may require monitoring, a dose adjustment, or separating the times you take each one. Consult your pharmacist before using them together.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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This information is for education only and is not a substitute for professional medical advice. Always check with your pharmacist or doctor before starting, stopping, or combining supplements and medications.